The objectives of this project are (1) to study the mechanism of mitogenic activities of growth factors based on their molecular conformation and (2) to develop and design specific and competitive peptide inhibitor of cell adhesion and migration during invasion. Results obtained so far include: (1) Four cyclic peptides, analogues of human epidermal growth factor (EGB) and transforming growth factor (TGF)-alpha, have been synthesized by high dilution method and purified by high performance liquid chromatography (HPLC). (2) Using a radioreceptor assay, all four of synthetic cyclic peptides competed binding of (125) I- EGF to the EGF receptor at a concentration of 100 uM. Cyclic (Ala(20)) EGF (14-31) and cyclic EGF (20-31) were able to block 30% and 20% of the binding of (125) I-EGF to the receptor, respectively. In the case of TGF-alpha, clycic (Ala(21)) TGF (16- 32) and cyclic TGF (21-32) would displace 20% and 11% of the (125) I-EGF to the receptor, respectively. (3) Using various two- dimensional nuclear magnetic resonance (NMR) techniques, the proton resonances of the individual amino acids for both TGF- 17mer and TGF-12mer were assigned, and the internuclear proton-proton distances through space were obtained. The latter information was used to generate energy-minimized peptide structures using the computer program. (4) Four cell recognition peptide analogues have been synthesized and purified. (5) Circular dichroism (CD) studies of GRGDS and GRGES in methanol reveal that GRGDS has a more highly ordered secondary structure. (6) The pK(a) value of Asp and Glu in the GRGXS series, determined by pH titration using CD spectroscopy, were 2.50 and 3.10, respectively, which were both lower than that of the individual amino acids (3.86 for Asp, 4.01 for Glu).